A melatonina, o ritmo circadiano, o núcleo supraquiasmático e a Glândula Pineal

Tem sido repetidamente demonstrado que as desordens da ritmicidade pode causar uma variedade de doenças, bem como danos aos processos envolvidos no metabolismo, responsáveis das doenças cardiovasculares e do cancro. Os ritmos do nosso corpo dependem de uma complexa rede hierarquicamente organizada pelo núcleo supraquiasmático (SCN) e da epifisi (glândula pineal). Até agora, diversas abordagens farmacológicas têm sido sugeridas, mas para restaurar um ritmo circandiano de maneira correcta, os melhores resultados foram obtidos através da administração de melatonina, demonstrou ser capaz de re-modular o relógio biológico.

Melatonin receptors as therapeutic targets in the suprachiasmatic nucleus.

Expert Opin Ther Targets. 2016 Apr 15;
Authors: Pévet P

INTRODUCTION: Disorders of rhythmicity can cause a variety of pathologies and are known to impair processes involved in metabolism, as well as in cardiovascular disease and cancer. Developing strategies to treat or prevent such diseases is a new challenge for medicine. Rhythms depend on a complex multi-oscillatory circadian network which, in mammals, is hierarchically organized with the suprachiasmatic nuclei (SCN) as master clock. The SCN, thus form an ideal structure for target discovery in circadian pathologies. Areas covered: The development of strategies to treat or prevent disorders of rhythmicity is a new challenge for medicine. Several pharmacological approaches have been suggested, but until now, it has been mostly melatonin (MTL) or MTL-agonists which have demonstrated usefulness in modulating clock activities in vivo. A great number of structurally different MTL receptor ligands have been developed, some of which are already approved and marketed as drugs. The MTL receptor involved in phase-shifting circadian rhythms (chronobiotic effect) is the MT1 subtype. Expert opinion: As the two receptor subtypes for MTL may have divergent functions, the development of highly selective MT1 and MT2 agonists (and antagonists) is key for the discovery of novel therapeutic agents in specifically defined circadian pathologies. The identification of cells expressing the different MTL receptor subtypes should also permit a better understanding of MLT physiology/pharmacology.

PMID: 27082492 [PubMed - as supplied by publisher]

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